Glucose test provenance recording in UK primary care: was that fasted or random?

AIMS: To describe the proportion of glucose tests with unrecorded provenance in routine primary care data and identify the impact on clinical practice. METHODS: A cross-sectional analysis was conducted of blood glucose measurements from the Royal College of General Practitioner Research and Surveillance Centre database, which includes primary care records from >100 practices across England and Wales. All blood glucose results recorded during 2013 were identified. Tests were grouped by provenance (fasting, oral glucose tolerance test, random, none specified and other). A clinical audit in a single primary care practice was also performed to identify the impact of failing to record glucose provenance on diabetes diagnosis. RESULTS: A total of 2 137 098 people were included in the cross-sectional analysis. Of 203 350 recorded glucose measurements the majority (117 893; 58%) did not have any provenance information. The most commonly reported provenance was fasting glucose (75 044; 37%). The distribution of glucose values where provenance was not recorded was most similar to that of fasting samples. The glucose measurements of 256 people with diabetes in the audit practice (size 11 514 people) were analysed. The initial glucose measurement had no provenance information in 164 cases (64.1%). A clinician questioned the provenance of a result in 41 cases (16.0%); of these, 14 (34.1%) required repeating. Lack of provenance led to delays in the diagnosis of diabetes [median (range) 30 (3-614) days]. CONCLUSIONS: The recording of glucose provenance in UK primary care could be improved. Failure to record provenance causes unnecessary repeated testing, delayed diagnosis and wasted clinician time.

Effect of hyperglycaemia on muscarinic M3 receptor expression and secretory sensitivity to cholinergic receptor activation in islets.

AIMS: Islets are innervated by parasympathetic nerves which release acetylcholine (ACh) to amplify glucose-induced insulin secretion, primarily via muscarinic M3 receptors (M3R). Here we investigate the consequence of chronic hyperglycaemia on islet M3R expression and secretory sensitivity of mouse islets to cholinergic receptor activation. METHODS: The impact of hyperglycaemia was studied in (i) islets isolated from ob/ob mice, (ii) alginate-encapsulated mouse islets transplanted intraperitoneally into streptozotocin-induced diabetic mice and (iii) mouse and human islets maintained in vitro at 5.5 or 16 mmol/l glucose. Blood glucose levels were assessed by a commercial glucose meter, insulin content by RIA and M3R expression by qPCR and immunohistochemistry. RESULTS: M3R mRNA expression was reduced in both ob/ob islets and islets maintained at 16 mmol/l glucose for 3 days (68 and 50% control, respectively). In all three models of hyperglycaemia the secretory sensitivity to the cholinergic receptor agonist, carbachol, was reduced by 60-70% compared to control islets. Treatment for 72 h with the irreversible PKC activator, PMA, or the PKC inhibitor, Gö6983, did not alter islet M3R mRNA expression nor did incubation with the PI3K-inhibitor, LY294002, although enhancement of glucose-induced insulin secretion by LY294002 was reduced in islets maintained at 16 mmol/l glucose, as was mRNA expression of the PI3K regulatory subunit, p85α. CONCLUSIONS: Cholinergic regulation of insulin release is impaired in three experimental islet models of hyperglycaemia consistent with reduced expression of M3 receptors. Our data suggest that the receptor downregulation is a PKC- and PI3K-independent consequence of the hyperglycaemic environment, and they imply that M3 receptors could be potential targets in the treatment of type 2 diabetes.